Regulation of retromer-dependent protein sorting in health and disease

Faculty Development Competitive Research Grant Program (General) 2024-2026

The long-term objective of our research is to understand how the sorting of internalized cell surface proteins is differentially regulated (recycling versus degradation) in response to metabolic and environmental signals and how the dysregulation of this process leads to human diseases, such as cancer. In the current project, we will focus on the retromer complex, which orchestrates protein sorting and recycling from the endosome. We have found that sorting nexin 3 (SNX3), an adaptor protein that is essential for recruiting the soluble retromer complex to the endosomal membrane for cargo engagement and retrograde trafficking, is regulated by arginine methylation. The project’s goal is to define how arginine methylation of SNX3 modulates SNX3 function and how this impacts normal retromer-dependent cargo recycling and colorectal cancer development.